RECOMBINANT-HUMAN-ERYTHROPOIETIN THERAPY FOR ANEMIC CANCER-PATIENTS ON COMBINATION CHEMOTHERAPY

Background: Patients with advanced cancer frequently experience clinic ally significant anemia, which is often exacerbated by myelosuppressiv e chemotherapy. Consistent with the anemia of chronic disease, studies have documented serum erythropoietin levels that are inappropriately low for the degree of anemia in cancer patients. Myelosuppressive chem otherapy impairs erythropoiesis, which may not fully recover between t reatment cycles. Recombinant human erythropoietin (rHuEPO) has been us ed safely and effectively to treat anemia in AIDS patients receiving z idovudine (AZT) and in patients with chronic renal failure. Purpose: T his study was designed to evaluate the clinical role of rHuEPO in redu cing symptomatic anemia in patients with advanced cancer who were rece iving myelosuppressive chemotherapy (excluding cisplatin). Methods: We studied 153 anemic cancer patients receiving cyclic combination chemo therapy in a prospective multicenter, double-blind, placebo-controlled trial. The patients were randomly assigned to receive either rHuEPO ( 150 U/kg) or placebo subcutaneously three times a week for a maximum o f 12 weeks or until the hematocrit level increased to 38%-40%. If the hematocrit reached this target level before 12 weeks, the rHuEPO dose could be reduced to maintain the hematocrit at that level for the dura tion of the study. Response to rHuEPO therapy was assessed by measurin g changes in hematocrit level, transfusion requirements, and quality o f life. Quality-of-life assessment was based on patients' responses to questionnaires before and after the courses of therapy. Results: The increase in hematocrit in the rHuEPO-treated group compared with hemat ocrit in the placebo-treated group was statistically significant (P = .0001) as measured by percentage point of change from baseline to fina l evaluation, by an increase in hematocrit level of six percentage poi nts or more unrelated to transfusion, and by a rise in hematocrit leve l to 38% or more unrelated to transfusion. There was a trend toward th e reduction in mean units of blood transfused per patient during month s 2 and 3 of therapy combined in rHuEPO-treated patients compared with placebo-treated patients (0.91 U versus 1.65 U; P = .056). In additio n, rHuEPO-treated patients experienced a statistically significant imp rovement in energy level and ability to perform daily activities (P le ss-than-or-equal-to .05). The two treatment groups showed no statistic ally significant differences in toxic effects except for increased inc idence of diaphoresis (P<.05) and diarrhea (P = .05) in the rHuEPO-tre ated group. Conclusions: We conclude that rHuEPO is safe and effective for reversing anemia related to advanced cancer or to chemotherapy fo r cancer.